Department of Pathology, University of New Mexico Health Science Center, Albuquerque, NM, USA; University of New Mexico Comprehensive Cancer Center, University of New Mexico Health Science Center, Albuquerque, NM, USA.
Division of Molecular Medicine, Department of Internal Medicine, University of New Mexico Health Science Center, Albuquerque, NM, USA.
J Steroid Biochem Mol Biol. 2024 Nov;244:106607. doi: 10.1016/j.jsbmb.2024.106607. Epub 2024 Aug 27.
Long-term administration of exogenous estrogen is known to cause urinary retention and marked, often fatal, bladder distention in both male and female mice. Estrogen-treated mice have increased bladder pressure and decreased urine flow, suggesting that urinary retention in estrogen-treated mice is due to infravesicular obstruction to urine outflow. Thus, the condition is commonly referred to as bladder outlet obstruction (BOO). Obesity can also lead to urinary retention. As the effects of estrogen are mediated by multiple receptors, including estrogen receptors ERα and ERβ and the G protein-coupled estrogen receptor (GPER), we sought to determine whether GPER plays a role in estrogen-induced BOO, particularly in the context of obesity. Wild type and GPER knockout (KO) mice fed a high-fat diet were ovariectomized or left ovary-intact (sham surgery) and supplemented with slow-release estrogen or vehicle-only pellets. Supplementing both GPER KO and wild type obese mice with estrogen for 8 weeks resulted in weight loss, splenic enlargement, and thymic atrophy, as expected. However, estrogen-treated obese GPER KO mice developed abdominal distension, debilitation, and ulceration of the skin surrounding the urogenital opening. At necropsy, these mice had prominently distended bladders and hydronephrosis. In contrast, estrogen-treated obese wild type mice only rarely displayed these signs. Our results suggest that, under conditions of obesity, estrogen induces BOO as a result of ERα-driven pathways and that GPER expression is protective against BOO.
长期给予外源性雌激素已知会导致雄性和雌性小鼠出现尿潴留和明显的、常致命的膀胱扩张。用雌激素处理的小鼠的膀胱压力增加，尿液流量减少，这表明雌激素处理的小鼠的尿潴留是由于下尿路流出受阻所致。因此，这种情况通常被称为膀胱出口梗阻（BOO）。肥胖也会导致尿潴留。由于雌激素的作用是通过多种受体介导的，包括雌激素受体 ERα 和 ERβ 以及 G 蛋白偶联雌激素受体（GPER），我们试图确定 GPER 是否在雌激素诱导的 BOO 中发挥作用，特别是在肥胖的情况下。给予高脂肪饮食的野生型和 GPER 敲除（KO）小鼠进行卵巢切除术或保留卵巢（假手术），并用缓释雌激素或仅载体制剂进行补充。用雌激素补充 8 周后，GPER KO 和野生型肥胖小鼠都出现体重减轻、脾脏肿大和胸腺萎缩，这是预期的结果。然而，用雌激素处理的肥胖 GPER KO 小鼠出现了腹部膨胀、虚弱和生殖器开口周围皮肤的溃疡。在尸检时，这些小鼠的膀胱明显扩张并伴有肾盂积水。相比之下，用雌激素处理的肥胖野生型小鼠很少出现这些症状。我们的结果表明，在肥胖的情况下，雌激素通过 ERα 驱动的途径诱导 BOO，而 GPER 的表达对 BOO 具有保护作用。
